rs398122519

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_002615.7(SERPINF1):​c.-9+2dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

SERPINF1
NM_002615.7 splice_region, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.86
Variant links:
Genes affected
SERPINF1 (HGNC:8824): (serpin family F member 1) This gene encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells. Mutations in this gene were found in individuals with osteogenesis imperfecta, type VI. [provided by RefSeq, Aug 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-1762114-G-GT is Pathogenic according to our data. Variant chr17-1762114-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 41893.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SERPINF1NM_002615.7 linkuse as main transcriptc.-9+2dupT splice_region_variant, intron_variant ENST00000254722.9 NP_002606.3 P36955A0A140VKF3
SERPINF1NM_001329904.2 linkuse as main transcriptc.-478+2dupT splice_region_variant, intron_variant NP_001316833.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SERPINF1ENST00000254722.9 linkuse as main transcriptc.-9+2dupT splice_region_variant, intron_variant 1 NM_002615.7 ENSP00000254722.4 P36955

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 6 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 01, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.58
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.58
Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs398122519; hg19: chr17-1665408; API